Cyclic RGD-Coated Ultrasmall Gd2O3 Nanoparticles as Tumor-Targeting Positive Magnetic Resonance Imaging Contrast Agents

The excellent theranostic properties of gadolinium oxide (Gd2O3) nanoparticles (GNPs) make them very useful as high-performance positive magnetic resonance imaging (T-1 MRI) contrast agents, X-ray computed tomography (CT) contrast agents, and gadolinium neutron capture therapy (GdNCT) agents in tumor targeting. Among these applications, tumor-targeting T-1 MRI is investigated in this study. To this end, we employ cyclic RGDs (cRGDs; cyclic Arg-Gly-Asp peptides) as tumor-targeting ligands to coat ultrasmall GNPs (particle diameter = 1.0-2.5 nm). Five types of commercial cRGDs are used in the coating. The cRGD-coated GNPs (cRGD-GNPs) are prepared through one-pot syntheses. They exhibit longitudinal water-proton relaxivity (r(1)) values of 10.0-18.7 s(-1)mm(-1), with r(2)/r(1) ratios of 1.4-1.7 (r(2) = transverse water-proton relaxivity), which are 3-5 times higher than those of commercial Gd chelates. The in vivo tumor targeting of the cRGD-GNPs is demonstrated by taking T-1 MR images in a model mouse with a liver tumor using one of the five cRGD-GNP sample solutions prepared. Approximately threefold contrast enhancements are observed in the T-1 MR images in the tumor region of the liver than in the normal part of the liver, following intravenous administration of the solution. These results demonstrate that cRGD-GNPs are potential tumor-targeting T-1 MRI contrast agents.